Guidelines for Thrombolysis and Thrombectomy in Acute Ischemic Stroke Management

Intravenous Thrombolysis with Alteplase

The American Heart Association recommends IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 min with initial 10% of dose given as bolus over 1 min) for eligible patients who can be treated within 4.5 hours of ischemic stroke symptom onset or last known well 1, 2
Treatment should be initiated as soon as possible after patient arrival and CT scan, with a target door-to-needle time of less than 60 minutes in 90% of treated patients, and a median door-to-needle time of 30 minutes 2, 3
Only assessment of blood glucose must precede the initiation of IV alteplase in all patients 1
For patients with acute ischemic stroke who awake with stroke symptoms or have unclear time of onset >4.5 hours from last known well, IV alteplase administered within 4.5 hours of stroke symptom recognition can be beneficial if MRI shows DWI-FLAIR mismatch 1, 4
Patients with acute ischemic stroke and acute hypertension who are otherwise eligible for IV thrombolysis should have their BP lowered below 185/110 mm Hg before IV thrombolysis is initiated 1, 5
For patients >80 years of age presenting in the 3- to 4.5-hour window, IV alteplase is safe and can be as effective as in younger patients 6
Within 3 hours from symptom onset, treatment of patients with mild ischemic stroke symptoms that are judged as non-disabling may be considered 6
IV alteplase is reasonable in patients with a seizure at the time of onset of acute stroke if evidence suggests that residual impairments are secondary to stroke and not a postictal phenomenon 6
IV alteplase may be reasonable in patients who have a history of warfarin use and an INR ≤1.7 6
Patients on direct oral anticoagulants (DOACs) should not routinely receive alteplase, though endovascular thrombectomy may be considered in these cases 3

Mechanical Thrombectomy

Patients should receive mechanical thrombectomy with a stent retriever or with direct aspiration if they meet all the following criteria:
Mechanical thrombectomy is also recommended between 6 and 24 hours in patients who have sizable mismatch between ischemic core (by CTP or MRI-DWI) and either clinical deficits or area of hypoperfusion (by CTP or MRI-PWI) 1, 4
Patients with clinically suspected large vessel occlusion (LVO) should have non-invasive angiography (e.g., CTA) 1, 5
Patients with acute ischemic stroke within 6–24 hours of time last known well who have a LVO in the anterior circulation should have advanced imaging (CTP or DW-MRI, with or without MRI perfusion) to determine eligibility for mechanical thrombectomy 1
Eligible patients should receive IV thrombolysis even if mechanical thrombectomy is being considered 1, 7
The technical goal of mechanical thrombectomy should be reperfusion to a modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b/3 1
In patients under consideration for mechanical thrombectomy, observation after IV alteplase to assess for clinical response should not be performed, as any delay to mechanical thrombectomy is associated with worse outcomes 8

Common Pitfalls and Caveats

Delays in evaluation and initiation of therapy should be avoided, as the opportunity for improvement is greater with earlier treatment 9, 10
Electrocardiography and other blood tests (complete cell count, serum electrolytes and creatinine, INR and partial thromboplastin time, serum troponin) should be obtained but should not delay the initiation of reperfusion therapy 1, 5
Tenecteplase administered as a 0.4-mg/kg single IV bolus has not been proven to be superior or non-inferior to alteplase but might be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion 7
The use of sonothrombolysis as adjuvant therapy with IV thrombolysis is not recommended 7

Thrombolysis After 4.5 Hours Based on Perfusion Studies

Evidence for Extended Window Thrombolysis

The American Heart Association recommends that for patients with unknown time of onset or wake-up stroke presenting beyond 4.5 hours, IV alteplase can be beneficial when MRI demonstrates DWI-FLAIR mismatch, with Level A evidence 11
The Canadian guidelines suggest that selection of patients for IV alteplase after 4.5 hours based on CT, CTA, and CTP remains unproven at this time, according to 2018 guidelines 11
The International Journal of Stroke guidelines recommend that consultation with a stroke specialist should be obtained when considering alteplase after 4.5 hours 11

Practical Algorithm for Extended Window Treatment

The American College of Radiology recommends obtaining perfusion imaging (CTP or MRI-DWI with perfusion) to identify salvageable tissue, with a strength of evidence of Level A 11, 12
The American Heart Association suggests confirming imaging criteria: ischemic core ≤70 mL, penumbra ≥10 mL, mismatch ≥20%, with Level A evidence 11
The International Journal of Stroke guidelines recommend excluding patients with extensive early infarct changes (ASPECTS score can be used), with a strength of evidence of Level A 11

Important Caveats

The American Heart Association recommends that patients with large vessel occlusion should be evaluated for mechanical thrombectomy (6-24 hour window) using perfusion imaging, with Level A evidence 11, 12
The International Journal of Stroke guidelines suggest that MRI scanning can be challenging to obtain urgently in emergency settings, which must be considered in decision-making, with a strength of evidence of Level A 11
The American College of Cardiology recommends that earlier treatment within the extended window is likely better, as the pooled analysis showed diminishing benefit approaching 270 minutes and potential harm beyond this, with a strength of evidence of Level B 13, 14

ASPECTS Threshold for Thrombolysis Outside the 4.5-Hour Window

Evidence-Based Threshold

The American Heart Association/American Stroke Association recommends an ASPECTS score ≥6 for endovascular therapy within 6 hours, which has been adopted for patient selection in extended window thrombolysis protocols 15
The American College of Cardiology notes that even patients with ASPECTS <6 can benefit from endovascular thrombectomy, but this does not extend to thrombolysis alone, where hemorrhage risk is the primary concern 16

Critical Caveats

The American Heart Association/American Stroke Association guidelines from 2007 suggest that within the standard 3-hour window, the ASPECTS threshold is less stringent, with early ischemic changes >1/3 MCA territory not independently associated with adverse outcomes when treatment occurred within 3 hours 17, 18
The European Stroke Organisation and European Society of Minimally Invasive Neurological Therapy guidelines suggest using pc-ASPECTS ≥8 for basilar artery occlusion treatment, though this is based on observational data 19

Standard Eligibility Criteria, Contraindications, and Dosing for Extended‑Window IV Alteplase

Eligibility Criteria (Physiologic Parameters)

Blood pressure must be < 185/110 mm Hg before initiating alteplase – per the American Heart Association/American Stroke Association thrombolysis guidelines. 20
Blood glucose must be ≥ 50 mg/dL (mandatory pre‑treatment laboratory check) – required to ensure safe administration of alteplase. 20

Absolute Contraindications

Absence of intracranial hemorrhage on baseline imaging – patients with any intracranial bleed are excluded from thrombolysis. 20
No recent major surgery, active bleeding, or coagulopathy – these conditions increase the risk of hemorrhagic complications with alteplase. 20

Dosing and Administration

Alteplase dose: 0.9 mg/kg (maximum 90 mg), with 10 % given as an IV bolus over 1 minute and the remaining 90 % infused over 60 minutes – the standard regimen recommended for acute ischemic stroke regardless of vessel location or NIHSS score. 20